This study has been transitioned to CTIS with ID 2024-512602-26-00 check the CTIS register for the current data. Evaluate the (cost-) effectiveness of ulipristal in comparison with standard surgical treatment for symptomatic uterine fibroids,…
ID
Source
Brief title
Condition
- Reproductive neoplasms female benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Outcomes with regard to patient:
1) Fibroid-specific quality-of-life, measured by the Uterine fibroid
symptom-questionnaire (UFS-QOL) symptom severity score (SSS) outcome at 24
months after randomization
Outcomes with regards to costs (using internet medical consumption
questionnaires; iMCQ):
1) Direct health care costs
2) Costs due to loss of productivity (absenteeism from work)
3) Patient costs (informal care, other care services paid for by patients
themselves)
Secondary outcome
Secondary outcomes with regard to patient:
1) What is the effect of the intervention on quality of life parameters, such
as pain, societal participation and sexual functioning?
2) What is the effect of the intervention on fibroid specific complaints such
as volume reduction (UPA group); amount of menstrual bleeding (PBAC-score) and
Hemoglobin level.
3) What is the re-intervention rate in both treatment groups and how many
patients choose for an intervention after treatment with UPA??
4) What is the effect on patient preference and satisfaction?
5) Which complications/side-effects occur?
6) What is the effect of UPA-usage on the blood results, regarding liver
function?
7) Which sub-groups benefit most within the study group (subgroup-analysis)
Background summary
Fibroids are the most common benign tumors in women of reproductive age,
occurring in up to 80% of the population, with 20-50% of those requiring
clinical intervention. Fibroids are therefore a major source of healthcare
costs: in the Netherlands around 7500 hysterectomies are performed for this
indication, with annual in-hospital costs of 30.000.000 euro*s. Up to now,
fibroid surgery is the gold standard, but not always preferable. Although
hysterectomy usually solves a lot of fibroid complaints, pregnancy is
impossible and long term complications such as stress-urinary-incontinence
(SUI) surgery can occur. Uterus-sparing surgeries are related to recurrence of
the fibroids or scarring of the uterus, which could also influence fertility
outcomes. For all three fibroid surgeries accounts that severe complications
can occur in 1 out of 100 patients during and after surgery, such as
haemorrhage, vesicoperitoneal fistula, ureteral injury, rectal perforation or
fistula.
Ulipristal Acetate (UPA) was introduced in 2012 as a new treatment option for
symptomatic uterine fibroids. UPA is a selective progesterone receptor
modulator with effect on fibroid volume and fibroid related complaints. The
effectiveness of UPA is evaluated in the PEARL trials. UPA was first evaluated
as a pre-treatment before surgical treatment of uterine fibroids.
Pre-treatment consisted of a daily 5 mg tablet during a 3 months period prior
to surgery leading to a median volume reduction of 36% (IQR 11-58%). Also
bleeding complaints decreased dramatically, leading to amenorrhea in 79% of the
patients and thereby offering a better pre-operative condition for patients.
Recently long-term treatment with UPA was evaluated in the PEARL III&IV trials.
In total four (3 months) treatment courses were administered separated by
treatment free intervals of 2 months. Quality of Life (QOL) scores were
obtained using the Uterine Fibroid Symptoms questionnaire (UFS-QOL), a
validated QOL tool for fibroid symptoms that breaks down to a Symptom Severity
Score (SSS) and a general QOL score. SSS (0-100) diminished from 50 to 16
points (70% improvement) and general QOL (0-100) improved form 57 to 84 (almost
50% improvement also). Volume reduction augmented during the courses up to 65%
after the fourth course. Amenorrhea rates were 74%, 73%, and 70% in women who
received treatment courses 2, 3, and 4, respectively.
UPA was launched as a revolutionary medication for fibroids, claiming to make
invasive treatment unnecessary. UPA is however quite costly and has never been
compared to other treatment modalities. Furthermore there is some concern about
the long-term effects on the endometrium. Very recently (November 2017), the
Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicine
Agency (EMA), started a procedure to investigate ulipristal, due to a possible
relation between the medicine and a very rare form of liver injury: Drug
Induced Liver Injury (DILI). The PRAC concluded that a possible relation
between ulipristal and DILI is unsure, but can't be excluded or proven.
Therefore they recommend risk-minimization measures to trace possible liver
injury in a very early stage and to ensure that this injury is reversibel.
These risk-minimazation measures are applied in our protocol and can be found
in chapter 6.4.1 'Summary of PRAC recommendations'.
This study aims to investigate the (cost-) effectiveness of UPA long term
administration in comparison to *standard* treatment for patients with moderate
to severe complaints due to uterine fibroids.
Study objective
This study has been transitioned to CTIS with ID 2024-512602-26-00 check the CTIS register for the current data.
Evaluate the (cost-) effectiveness of ulipristal in comparison with standard
surgical treatment for symptomatic uterine fibroids, measured by the symptom
severity score of the Uterine Fibroid Symptoms questionnaire (UFS-QOL), a
validated Quality of life tool for fibroid symptoms. Also, a cost-effectiveness
analysis will be performed.
Study design
Randomized controlled multi-center trial with 24 months of follow-up
Intervention
Ulipristal, 3-4x 3-month period of daily intake of one tablet of Ulipristal 5
mg, followed by a 2-month period of no intake.
Study burden and risks
The burden for the patients is mainly the completing of the questionnaires
(baseline, 3, 6, 12, 18 and 24 months follow up) and the extra telephone
appointment at 18 months of follow up. In the ulipristal group and the patients
who had a myomectomy/embolization will have recurrent visits with their
gynaecologist at 6 (only by telephone) 12 and 24 months of follow up. These
visits are standard care and not extra in this study. Patients who had a
hysterectomy will have telephone appointments at 6, 12, 18 and 24 months of
follow up, this is extra in this study.
Recent post-marketing data showed a possible relation between ulipristal and a
very rare form of liver injury, therefore riskminimazation measures were
implemented (nationally), which have been applied in this trial to ensure
safety. Therefore, this is also standard care, women not participating in this
trial are also tested. The estimated risk is <1:95.000 patients. By monthly
livertesting, the risk is minimized, as possible liver injury is traced in a
very early stage.
The burden and chance on risks for the participating patients are very low.
Both treatment options are widely implemented in the Netherlands en tested for
safety in scientific research. Important to keep in mind is that both treatment
options are implemented, but never compared to eachother. The extra burden is
low, because both treatment options (also outside this trial) are accompanied
by normal control visits and in case of ulipristal: regular bloodtesting.
Patients allocated to the ulipristal group are not exposed to the risks that
are asociated with surgery. Patients allocated to surgery are not exposed to
the possible risk associated with ulipristal (most importantly: possible liver
injury). For an extensive risk analysis we like to refer to the research
protocol, chapter 13 'Structured Risk Analysis.
In chapter 8 'Methods' and the Patient information folder (pamflet), you can
also find a clear schedule which appointments and procedures are standard care
and which ones are extra in this trial.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
Women visiting the gynaecological outpatient clinic with symptomatic fibroids
will be screened for eligibility. In order to be eligible to participate in
this trial, a subject must meet all of the following criteria:
- Symptomatic fibroids warranting surgical treatment, either hysterectomy,
myomectomy or uterine artery embolization
- Conservative treatment failed or is undesired
- Pre-menopausal
- 18 years of age, or older
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- Asymptomatic fibroids
- Current pregnancy or unwillingness to use contraception
- Suspicion of malignancy
- Current use of ulipristal
- Contra-indication for the use of ulipristal
o History of, or present liver disease or hepatic impairment;
o Transaminases (alanine transaminase (ALT) or aspartate
aminotransferase (AST) and/or
total bilirubin exceeds 2 times the upper limit of normal
(performed within a month prior to
inclusion).
o Medication that interacts with ulipristal:
* Moderate CYP3A4 inhibitors (e.g. erythromycin, grapefruit
juice, verapamil)
* Potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir,
nefazodone, itraconazole,
clarithromycine)
* Potent CYP3A4 inducers (e.g. rifampicin, carbamazepine,
phenytoin, phenobarbital,
St. John*s wort, efavirenz)
- Not willing or able to give written informed consent
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-512602-26-00 |
| EudraCT | EUCTR2017-005120-16-NL |
| Other | Nederlands Trial Register: 6860 |
| CCMO | NL62638.029.18 |